Miancheng Zou

Chemical synthesis of antimicrobials ESR 1.3

Double warhead antibiotics

In recent years our group has developed a powerful technique to functionalize complex natural products without the need for multistep organic synthesis. We employ aptamers based on nucleic acids that bind a complex target structure. The functional groups in contact with the aptamer are protected while functional groups of the target not in contact with the aptamer can be regioselectively modified (Nature Chem. 2012, 4: 789, Figure 1). As a consequence, many new antibiotic derivatives based on aminoglycosides were fabricated that would have required years to be synthesized by conventional procedures. We prognosticate that the aptamer protective group (APG) technology will have great impact on natural product-based drug development and lead optimization. During the ALERT program, novel antibiotics are designed and synthesized employing APGs to overcome antibacterial resistance or to fabricate conjugates composed of different classes of antibiotics exhibiting two antimicrobial warheads.